Induction of Immunological Antitumor Effects by Adenovirus-Mediated Gene Transfer of B7-1 in a Murine Squamous Cell Carcinoma Cell Line

Hoshitani, Yasuhiko MD
Ishida, Haruhiko MD, PhD
Otsuki, Naoki MD, PhD
Shirakawa, Toshiro MD, PhD
Gotoh, Akinobu MD, PhD
Nibu, Ken-ichi MD, PhD

Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine (Drs Hoshitani, Ishida, Otsuki, and Nibu), International Center for Medical Research and Treatment, School of Medicine (Dr Shirakawa), Kobe University, Kobe, Japan; and Division of Cell and Gene Therapy, Institute for Advanced Medical Science, Hyogo College of Medicine, Hyogo, Japan (Dr Gotoh).

Correspondence: Ken-ichi Nibu, MD, PhD, Department of Otolaryngology–Head and Neck Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-Cho, Chuo-ku, Kobe 650-0017, Japan ([email protected]).

Author Contributions: Dr Nibu had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Hoshitani, Ishida, Shirakawa, Gotoh, and Nibu. Acquisition of data: Hoshitani. Analysis and interpretation of data: Hoshitani, Ishida, Otsuki, Gotoh, and Nibu. Drafting of the manuscript: Hoshitani. Critical revision of the manuscript for important intellectual content: Ishida, Otsuki, Shirakawa, Gotoh, and Nibu. Obtained funding: Ishida, Gotoh, and Nibu. Study supervision: Ishida, Otsuki, Shirakawa, Gotoh, and Nibu.

Financial Disclosure: None reported.

Funding/Support: This work was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science for Dr Ishida (grant 16591707) and for Dr Nibu (grant 18659500) and a Health and Labour Sciences Research Grant for Clinical Cancer Research from the Japan Ministry of Health, Labour, and Welfare for Dr Nibu (grant H17-Gannrinshou-001).

Submitted for Publication: September 21, 2006; accepted November 7, 2006.

Archives of Otolaryngology -- Head & Neck Surgery 133(3):p 270-275, March 2007.

Objective

To evaluate the antitumor immune effects of B7-1 gene expression mediated by adenoviral vectors against squamous cell carcinoma. Transfection of the costimulatory molecule B7-1 gene into certain murine tumors increases antitumor immunity and suppresses tumor growth.

Design

In vitro and in vivo study.

Interventions

A murine squamous cell carcinoma cell line, KLN205, was infected with adenoviral vectors carrying either B7-1 (AdB7) or LacZ (AdCL) genes. Infected cells were injected subcutaneously into the flanks of DBA/2 mice.

Main Outcome Measures

The growth of tumors infected with adenviral vectors was measured.

Results

AdB7-infected cells grew significantly slower than AdCL-infected cells in vivo, while there was no significant difference in the growth rates between the 2 groups in vitro. Moreover, significant growth suppression of rechallenged noninfected parental cells was observed in the mice immunized with AdB7-infected cells but not in those immunized with AdCL-infected cells.

Conclusion

These results suggest that the B7-1 gene has therapeutic potential for immunotherapy against head and neck squamous cell carcinoma.